Inflammation also affects iron metabolism at many levels. Inflammatory cytokines can lead to reduced serum concentrations of iron and transferrin. Reduction in transferrin then leads to decreased iron absorption via the gut. Lactoferrin in polymorphonuclear cells can act as an iron scavenger with bactericidal activity. Lactoferrin levels have been shown to increase in inflammation and can bind large amounts of free iron, thereby reducing overall availability. Functional iron deficiency, which is also a characteristic the inflammatory state associated with erythropoietin resistance is defined as low availability of iron for erythropoiesis despite normal or high iron stores. Functional iron deficiency can occur in two ways; when high doses of exogenous erythropoietin stimulate erythropoiesis and it exceeds the capacity to deliver adequate iron or alternatively, when delivery of iron from the reticuloendothelial system to hematopoietic cells is blocked. Both mechanisms may occur in patients with chronic inflammation and erythropoietin resistance.